Reports:unscear2008AnnexDAppendexD
UNCSEAR 2008 AnnexD AppendixD Late Health Effects III Late health effects of the Chernobyl accident in workers and the general public C. Empirical Studies on specific diseases 4. Leukaemia (a) Introduction D160. Studies such as those of the survivors of the atomic bombings have demonstrated that leukaemia can be induced by ionizing radiation delivered at high doses and dose rates U1. Further, leukaemia is one of the cancers most sensitive to induction by ionizing radiation and has the shortest minimum induction period of any such cancer, of the order of two years. Detailed analysis of the latest data on the survivors of the atomic bombings, shows that in terms of relative risk, the risks are highest for those exposed at an early age, and follow a wave pattern with time after exposure. The fall in risk with time since exposure occurs more rapidly among those exposed at an early age than among those exposed at a later age. Therefore, studies relevant to the Chernobyl accident have to be reviewed according to age at the time of exposure. D161. Analysis of pooled data from several studies of nuclear workers C10 have yielded estimates of leukaemia risk that are consistent with those from studies of the survivors of the atomic bombings. In this pooled analysis, the selected nuclear workers were monitored for exposure to external radiation on a monthly or yearly basis and, consequently, might be expected to provide a better estimate of any effect due to dose rate. However, despite the huge number of workers involved in this pooled analysis, the confidence intervals in relation to the estimated leukaemia risk remain very large; the ERR was 1.93 (95% CI: <0, 8.47) Sv–1 and was not statistically significant. So, the effect of protracted radiation exposure on leukaemia risk and, in particular, the magnitude of any dose and dose‑rate effectiveness factor (DDREF) U3 are matters that still need to be resolved. The non‑linear dose–response relationship for leukaemia, particularly that seen in the survivors of the atomic bombings, should be taken into account when discussing values for the DDREF. D162. The population exposed as a result of the Chernobyl accident includes the recovery operation workers, some of whom were exposed at high or moderate dose rates (depending on when they worked on the industrial site), and members of the general population, who have been subject to exposures at low dose rates (primarily from 137Cs) for a number of years and will continue to be exposed in this manner in the future. Thus, the risk of leukaemia in the exposed population is a matter both of public health concern and scientific interest. A number of studies have been reported in which the incidence of leukaemia in various subgroups of the population have been examined. D163. Studies of leukaemia incidence in those exposed in utero or at an early age as a consequence of the accident have been reported specifically, in view of the increased susceptibility of such individuals to radiation‑induced leukaemia. These studies are discussed first, followed by more general studies of those exposed as adults. Some of the more general studies presumably include those exposed as children or adolescents, since results with respect to age at exposure are not always presented separately in these studies. (b) Assessment of current evidence for those exposed in utero D164. Several geographical correlation studies were available in the UNSCEAR 2000 Report U3 which compared leukaemia rates in those exposed in utero with those not so exposed. These studies did not provide any convincing evidence of a measurable association, with the possible exception of the study in Greece P9. Rates of leukaemia in those exposed in utero and those born either before the accident or a year after, differed by a factor of 3. However, the numbers of cases in each exposure category were small. Furthermore, a similar study design was applied to the inhabitants of other countries exposed to radioactive deposition, but the findings were negative S8. D165. Since then, a further study has been published by Noshchenko et al. N9 comparing the cumulative incidence of leukaemia amongst those exposed in utero in a highly contaminated area of Ukraine with that in one with lower levels of radioactive deposition. This yielded a relative risk of 2.7 (95% CI: 1.9, 3.8) for all leukaemias. The number of cases available for analysis was not large (21 in the exposed area and 8 in the control area), and the descriptive nature of the study limits the interpretation that can be placed on this estimate. D166. Information on infant leukaemia rates following the accident has been evaluated by the UK Committee Examining Radiation Risks of Internal Emitters (CERRIE) C24. Whilst the data from Great Britain were too sparse for firm conclusions to be drawn, CERRIE concluded that the findings on infant leukaemia in various countries after the Chernobyl accident do not provide sufficient persuasive evidence that the risk of internal exposure to radionuclides is seriously underestimated by using risk estimates obtained from studies of exposure in utero to sources of external radiation C24. © Assessment of current evidence for those exposed as children D167. In the UNSCEAR 2000 Report U3, a number of geographical correlation studies of leukaemia incidence occurring in populations exposed as children to radiation resulting from the Chernobyl accident were reviewed. These studies provided little or no evidence of any increase in leukaemia risk due to the radiation exposure. D168. Since the UNSCEAR 2000 Report, similar geographical correlation studies, which compared rates of leukaemia before and after the accident among those exposed as children, have again provided no support for the hypothesis of a measurable increase in leukaemia risk in Belarus G5, the Russian Federation I24 or Hungary T4. D169. In addition to the geographical correlation studies, the results of two analytical studies of leukaemia occurring amongst those exposed in childhood have appeared N10. In the first case‑control study N10, carried out in Ukraine, all cases of leukaemia among those aged 0–20 years at the time of the accident were diagnosed in the Rivne and Zhytomyr oblasts between 1987 and 1997. Controls were selected from the same two oblasts, but from districts other than those that provided the cases, and they were matched by age at exposure, sex and type of settlement. The mean cumulative bone marrow dose to all study subjects was very small (4.5 mSv). A total of 98 out of 272 potentially eligible cases were independently confirmed and interviewed; no explanation was given for the method of their selection. Statistically significant associations were found for acute leukaemia between 1993 and 1997 among males with doses of 10 mSv or more, and for acute myeloid leukaemia among those diagnosed between 1987 and 1992. Possible biases in the selection of cases and controls cast doubts about the findings of this study U1, W5. D170. The larger case‑control study reported in reference D5 was conducted in the three republics, and included cases from the earlier study N10 as a subset. This study showed mixed results: those from the Ukraine data showed a significant association of leukaemia risk with the radiation exposure; those from the Belarus data showed a non‑significant association; and those from the Russian Federation data showed no association. The ERRs in the three countries were 78.8, 4.09 and ‑4.94 Gy–1, respectively. Because radiation doses were very low (median dose was less than 10 mGy), the statistical power of the analyses was diminished U1. The authors concluded that “this study provides no convincing evidence of an increased risk of childhood leukaemia as a result of exposure to Chernobyl radiation” D5. D171. Thus, overall, so far there are few studies available and little convincing evidence to suggest a measurable increase in the risk of leukaemia among those exposed as children to the radiation resulting from the accident at Chernobyl. This conclusion is consistent with the earlier cancer registry studies of childhood cancer risk in Europe following the Chernobyl accident P12. (d) Assessment of current evidence for those exposed as adults D172. General population groups. A few studies of leukaemia incidence in groups of people exposed as adults to radiation resulting from the Chernobyl accident were available in the preparation of the UNSCEAR 2000 Report U3. Again, none of these studies provided persuasive evidence of any measurable effect. The majority of the geographical correlation studies conducted in various countries relied on the data available from national registries and showed no convincing evidence of any trends of increasing incidence of leukaemia. D173. Emergency and recovery operation workers. In 1996, a large cohort study of the Russian recovery operation workers (>142,000) was reported by Ivanov et al. I11. A total of 48 cases of leukaemia, including chronic lymphatic leukaemia (CLL), were diagnosed in the period 1986–1993 in the cohort. A statistically significant SIR of 1.77 (95% CI: 1.22, 2.47) was estimated comparing the rates of leukaemia in this cohort to the rates in the Russian population for 1990–1993. The value of the SIR estimated using population rates from before 1990 as a comparison was much lower and not statistically significant. A statistically significant ERR of 4.3 (95% CI: 0.83, 7.75) Gy–1 was estimated from the data. Risk estimation was based on a comparison of the observed incidence with the national incidence of leukaemia for males of the same age groups. This estimate appeared comparable in magnitude with the leukaemia risk estimate derived from data on the survivors of the atomic bombings who were older than 20 years of age at the time of the bombings (ERR = 3.70 Sv‑1, averaged over sexes) U3. However, it should be noted that the estimate in the Ivanov et al. study I11 included cases of CLL (n = 10). D174. In a further study of the Russian recovery operation workers, Ivanov et al. I13 studied the occurrence of leukaemia in a cohort of 71,870 workers engaged in recovery operations within the 30‑km zone between 1986 and 1990, and for whom estimates of individual external radiation doses were available from the Russian national dosimetric registry. They observed 58 cases of pathologically confirmed leukaemia between 1986 and 1998. After excluding CLL (n = 16), the type of leukaemia thought not to be induced by radiation, they obtained an SIR of 2.5 (90% CI: 1.3, 3.7) comparing those who incurred doses of 150–300 mGy with those who incurred doses below 150 mGy; they estimated an ERR of 6.7 (90% CI: 0.8, 23.5) Gy–1. D175. An earlier case‑control analysis from the same registry initially showed no significant trend with dose for all leukaemias, or for leukaemia excluding CLL, among the recovery operation workers who worked in the 30‑km zone in 1986–1987 I10; however a later analysis estimated significant ERRs ranging from 0.28 Gy–1 to 15.59 Gy–1 for essentially the same groups K11. In the latter study, a total of 36 non‑CLL cases diagnosed between 1986 and 1993 were compared with controls (case : control ratio = 1:3). The mean doses for cases were lower than those for the corresponding controls, but nevertheless an elevated (but not statistically significant) relative risk was observed in the highest dose group. D176. The results from these studies have been questioned, see reference U3. In discussing the discrepancy between the findings of the case‑control and cohort studies, Boice and Holm B46 suggested that the increased incidence observed in the cohort analyses reflected a difference in case ascertainment between the recovery operation workers and the general population and not an effect of radiation exposure. The magnitude of the risk is also questionable because of the large uncertainties in the “official” doses from the Russian State Chernobyl Registry and the procedures used to verify leukaemia cases were unknown. D177. Buzunov et al. B13 studied the incidence of leukaemia in 1987–1993 in a group of approximately 175,000 recovery operation workers in Ukraine. They compared the rates of leukaemia in those first employed in 1986 and those employed in 1987, when doses were lower. They found that the rate of leukaemia was approximately double in the first group, but dose dependence within the groups was not studied. D178. Two other albeit smaller cohorts of recovery operation workers were followed. In the initial study, Rahu et al. reported no cases of leukaemia in the cohort of Estonian recovery operation workers who worked during 1986–1993 R3. In the second study, which involved follow‑up of the Estonian and Latvian recovery operation workers until 1998 R7, the incidence of leukaemia in the Estonian workers remained unchanged, but that in the Latvian workers was significantly higher compared to the age‑matched general population (SIR = 2.59; 95% CI: 1.04, 5.34; n = 7 cases). The overall leukaemia excess, however, was not significantly increased (SIR = 1.53; 95% CI: 0.62, 3.17); and the authors were concerned that “ascertainment bias stemming from increased awareness and medical attention may increase false‑positive diagnoses of leukaemia, and hence explain the excess number of cases in the Latvian cohort.” D179. Two case‑control studies of recovery operation workers—one using data from Belarus, the Russian Federation and the Baltic countries, and the other data from Ukraine—were conducted H11. Both utilized the same questionnaire and had the same nested case‑control design, with both cases and controls having been drawn from the cohorts of recovery operation workers in each country. The cohorts were assembled on the basis of the national Chernobyl State Registries. Both studies used the same method of dose reconstruction (RADRUE) based on interviews and various measurements of dose fields in the 30‑km zone around Chernobyl B11. The Committee was informed that the unpublished results of both studies indicate similar non‑significant increases in both non‑CLL and CLL leukaemia. This is somewhat surprising in view of the lack of any significantly increased radiation risk for CLL observed in most other studies. The Committee has recently concluded that CLL is not established as being caused by ionizing radiation U1. (e) Conclusions D180. The interest in leukaemia arises because of its known sensitivity to induction by ionizing radiation and also because of its short latent period. So far, no persuasive evidence has been found to suggest that there is a measurable increase in the risk of leukaemia among those exposed in utero and as children. This is not unreasonable given that the doses involved were generally very small, and therefore epidemiological studies would lack sufficient statistical power for an effect to be observed. D181. Amongst adults, the most meaningful evidence comes from the studies of recovery operation workers. At present, there is some evidence of a detectable effect among a group of recovery operation workers from the Russian Federation, but this is far from conclusive. It would therefore be premature to make a direct comparison between the data obtained from these studies directly with the risk estimates obtained from studies involving high doses and dose‑rate (such as of the survivors of the atomic bombings). The limitations discussed earlier of the studies of the recovery operation workers must be borne in mind. Nevertheless, future results from studies of the recovery operation workers will, hopefully, provide meaningful data that can be compared with those from other studies. References B11 Bouville, A., V.V. Chumak, P.D. Inskip et al. The chornobyl accident: estimation of radiation doses received by the Baltic and Ukrainian cleanup workers. Radiat. Res. 166(1): 158-167 (2006). 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